Joint iNANO & DANDRITE Topical Seminar

Joint iNANO & DANDRITE Topical Seminar
by guest researcher Arek Kulczyk
Thursday 30 April 2015
13.15 – 14.00
The iNANO Auditorium
The Interdisciplinary Nanoscience Center
Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C
Arek Kulczyk
Harvard University
Dept. Biological Chemistry and Molecular Pharmacology
Boston, Massachusetts, USA
Single-molecule studies of the replisome structure and dynamics
We present the first structures of a replisome assembled on DNA resembling a replication fork. The
four structures determined by single-particle cryo-electron microscopy (cryo-EM) represent
different functional states of the megadalton-sized bacteriophage T7 replisome. The replisome
consists of DNA helicase, RNA primase, and two DNA polymerase molecules. The two molecules of
DNA polymerase adopt different spatial arrangement at the replication fork reflecting their roles in
leading- and lagging-strand synthesis. Structures in combination with biochemical data reveal
fundamental molecular mechanisms for leading-strand synthesis, formation and release of the
lagging-strand replication loop, and coordination of leading- and lagging-strand synthesis.
Using the single-molecule microscopy methods we identified interactions between the replication
proteins that orchestrate exchange of DNA polymerases at the replication fork. Since mechanisms
of DNA replication are highly conserved the observations are relevant to other replication systems.
In collaboration with Arne Moeller, we plan to refine structures of the replisome to high resolution
using the state-of-the-art cryo-EM facility in the Interdisciplinary Nanoscience Center.
E-mail: Arek@hms.harvard.edu
Website: https://www.linkedin.com/pub/kulczyk-arek/10/881/442
Host: Arne Möller, Team Leader at DANDRITE and Assistant Professor at iNANO, Aarhus University
Danish Rese arch Institute of Translational Ne uroscie nce - DANDRITE
Nordic-EMBL Partnership for Molecu lar Medicine
www.dandrite.au.dk
The Interdisciplinary Nanoscience Ce nter - iNANO
www.inano.au.dk/news-events